Protective effect of berberine against cardiac ischemia/reperfusion injury by inhibiting apoptosis through the activation of Smad7

Berberine (BBR) is an isoquinnoline derivative alkaloid extracted from Rhizoma Coptidis that has the potential to protect myocardial tissues from ischemia/reperfusion (I/R) injuries. We attempted to evaluate the effect of BBR on the proliferation and apoptosis of a hypoxia/reoxygenation (H/R) cell model and to reveal the mechanism driving the improving function of BBR myocardial tissues. The H/R cell model was established using H9c2 rat cardiac myoblasts. The cell viability, apoptotic rates, and cell cycle distribution were measured with CCK-8 assay and flow cytometry. The expression of Smad7 and caspase-3 were determined both at mRNA and protein levels. In addition, expression of Smad7 was knocked down with specific siRNA and the effect of the interference was assessed. The proliferation ability of H/R cells was enhanced after the administration of BBR, and the apoptosis and cell cycle arrest due to H/R injury were also alleviated by BBR treatment. Moreover, the treatment of BBR on H/R injury functioned through the Smad7-activation-induced attenuating of apoptosis by activating Smad7 pathway which resulted suppression of caspase 3 expression and activity. The knockdown of Smad7 confirmed our conclusion about the key role of Smad7 in the function of BBR administration. However, our results as well as some previous studies also demonstrated that the effect of BBR was tissue and protocol specific, and the underlying mechanism related to the BBR treatment was so complicated that practical application should be carefully investigated based on certain diseases and patients.